Ochratoxin A is a mycotoxin that causes nephropathy in a variety of animals, including swine, and may be the causative agent of a disease in humans called Balkan endemic nephropathy. Symptoms of the disease that are specific for the toxin have been difficult to gather. We have found that renal phosphoenolpyruvate carboxykinase (PEPCK) activity, which is located in the proximal tubules, is blocked in rats fed low doses (20 ug) of the toxin for two days. No other enzyme activity that have measured is affected. In this proposal, we wish to test whether renal PEPCK activity in swine is an early and selective indicator of ochratoxin A-induced nephropathy. The choice of swine as the animal model is based on the similarity of clinical and pathological symptoms following exposure to ochratoxin A, and human Balkan endemic nephropathy. We will measure PEPCK activity in renal biopsies of swine fed graded doses of ochratoxin A, over a one month period. We will assess the effect of ochratoxin A by using the rations of toxin-sensitive (PEPCK) and insensitive (pyruvate carboxylase, gamma-glutamyl transpepidase) enzyme activities, since the biopsy may contain portions of medulla as well as outer cortex. Changes in enzyme activity will be compared to other parameters of renal function that are known to be affected by ochratoxin A, such as glucosuria, the ability to concentrate urine, and renal histology. We will also determine whether renal PEPCK activity in rats is affected by two known nephrotoxins, citrinin and mercury, in order to confirm the specificity of action of ochratoxin A. Our general goal is to develop a selective and sensitive biochemical method to detect human Balkan endemic nephropathy.